Apparatuses and methods for manipulating droplets

• US 9,638,662 B2
• Filed: 08/04/2015
• Issued: 05/02/2017
• Est. Priority Date: 09/24/2002
• Status: Expired due to Fees

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Pollack, Michael G., Pamula, Vamsee K., Fair, Richard B.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US14/817,834
• Publication Number:
  US 20150336098A1
• Time in Patent Office: 637 Days
• Field of Search: 422502, 422504
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0424 Dielectrophoretic forces
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B81B 2201/058 Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81B 3/0021 : Transducers for transforming electrical into mechanical energy or vice versa dynamo-electric machines H02K99/00; electrostatic machines H02N1/00; piezoelectric devices H10N30/00
• CPC Class Codes: B81C 1/00119 : Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
• CPC Class Codes: C12Q 1/6846 : Common amplification features
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 27/44769 : Continuous electrophoresis, i.e. the sample being continuously introduced, e.g. free flow electrophoresis [FFE]
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G05D 7/0694 : by action on throttling means or flow sources of very small size, e.g. microfluidics microvalves F16K99/0001; microstructural devices per se B81B
• CPC Class Codes: H01L 21/6715 : Apparatus for applying a liquid, a resin, an ink or the like H01L21/67126 takes precedence
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Apparatuses and methods for manipulating droplets are disclosed. In one embodiment, an apparatus for manipulating droplets is provided, the apparatus including a substrate, multiple arrays of electrodes disposed on the substrate, wherein corresponding electrodes in each array are connected to a common electrical signal, and a dielectric layer disposed on the substrate first side surface and patterned to cover the electrodes.

Claims

1. A method for actuating a droplet, the method comprising the steps of:

(a) providing a droplet on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the droplet is initially disposed on a first one of the electrodes and is adjacent to a second one of the electrodes separated from the first electrode by a first gap;

(b) providing an electrical input in connection with the array of electrodes in a manner that permits a voltage to be applied to one or more of the electrodes in the array; and

(c) biasing the first electrode to a first voltage and the second electrode to a second voltage different from the first voltage whereby the droplet moves towards the second electrode.

2. The method according to claim 1 wherein the second voltage is a ground state.

3. The method according to claim 1 wherein the applied bias is either DC or AC.

11. The method according to claim 1 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.

4. A method for actuating a droplet, the method comprising:

(a) providing a droplet on a surface of a printed circuit board substrate, the surface comprising an array of drive electrodes and an at least substantially co-planar array of one or more reference elements, herein the droplet is disposed on a first one of the drive electrodes;

(b) providing an electrical input in connection with the array of drive electrodes in a manner that permits a voltage to be applied to one or more of the drive electrodes in the array; and

(c) biasing the first drive electrode to move the droplet from the first drive electrode to a second drive electrode.

5. The method according to claim 4 wherein the second electrode is adjacent to the first electrode along a first direction, the electrode array comprises one or more additional electrodes adjacent to the first electrode along one or more additional directions, the droplet is adjacent to the one or more additional electrodes, and the method comprises the steps of:

(a) selecting the first direction as a desired direction along which the droplet is to move; and

(b) selecting the second electrode for biasing based on the selection of the first direction.

12. The method according to claim 4 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.

6. A method for actuating a droplet, the method comprising:

(a) providing a droplet between a surface of a printed circuit board substrate and an elongate reference element substantially parallel to and spaced apart from the printed circuit board surface, wherein the printed circuit board surface comprises an array of drive electrodes and the droplet is disposed on a first one of the drive electrodes;

(b) providing an electrical input in connection with the array of drive electrodes in a manner that permits a voltage to be applied to one or more of the drive electrodes in the array; and

(c) biasing the first drive electrode to move the droplet from the first drive electrode to a second drive electrode.

13. The method according to claim 6 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.

7. A method for actuating a droplet, the method comprising:

(a) providing a droplet between a surface of a first printed circuit board substrate and a surface of a second printed circuit board substrate substantially parallel to and spaced apart from the printed circuit board, wherein the first printed circuit board surface comprises an array of drive electrodes and the droplet is disposed on a first one of the drive electrodes, and further wherein the second printed circuit board surface comprises an array of drive electrodes and an array of one or more reference elements;

(b) providing an electrical input in connection with the array of drive electrodes in a manner that permits a voltage to be applied to one or more of the drive electrodes in the array; and

(c) biasing the first drive electrode to move the droplet from the first drive electrode to a second drive electrode.

14. The method according to claim 7 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.

8. A method for merging two or more droplets into one droplet, comprising the steps of:

(a) providing first and second droplets on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the electrode array comprises at least three electrodes comprising a first outer electrode, a medial electrode adjacent to the first outer electrode, and a second outer electrode adjacent to the medial electrode, the first droplet is disposed on the first outer electrode and is adjacent to the medial electrode, and the second droplet is disposed on the second outer electrode and is adjacent to the medial electrode;

(b) selecting one of the three electrodes as a destination electrode;

(c) selecting two or more of the three electrodes for activation and de-activation based on the selection of the destination electrode; and

(d) activating and de-activating the electrodes selected to move one of the first and second droplets toward the other droplet or both of the first and second droplets toward each other, whereby the first and second droplets merge together to form a combined droplet on the destination electrode.

15. The method according to claim 8 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.

9. A method for splitting a droplet into two or more droplets, comprising the steps of:

(a) providing a starting droplet on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the electrode array comprises at least three electrodes comprising a first outer electrode, a medial electrode adjacent to the first outer electrode, and a second outer electrode adjacent to the medial electrode, and the starting droplet is initially disposed on at least one of the three electrodes and is adjacent to at least one other of the three electrodes;

(b) providing an electrical input in connection with the array of electrodes in a manner that permits a voltage to be applied to one or more of the electrodes in the array;

(c) biasing each of the three electrodes to a first voltage to position the starting droplet across the three electrodes; and

(d) biasing the medial electrode to a second voltage different from the first voltage to split the starting droplet into first and second split droplets, whereby the first split droplet is formed on the first outer electrode and the second split droplet is formed on the second outer electrode.

16. The method according to claim 9 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.

10. A method for splitting a droplet into two or more droplets, comprising the steps of:

(a) providing a starting droplet on a surface of a printed circuit board substrate, the surface comprising an array of electrodes, wherein the electrode array comprises at least three electrodes comprising a first outer electrode, a medial electrode adjacent to the first outer electrode, and a second outer electrode adjacent to the medial electrode, and the starting droplet is initially disposed on at least one of the three electrodes and at least partially overlaps at least one other of the three electrodes;

(b) providing an electrical input in connection with the array of electrodes in a manner that permits a voltage to be applied to one or more of the electrodes in the array;

(c) biasing the medial electrode to a first voltage to position the starting droplet, whereby the starting droplet at least partially overlaps the three electrodes; and

(d) biasing the medial electrode to a second voltage and at least one of the first and second outer electrodes to a third voltage, the second and third voltages different than the first voltage, to split the initial droplet into first and second split droplets, whereby the first split droplet is formed on the first outer electrode and the second split droplet is formed on the second outer electrode.

17. The method according to claim 10 wherein the printed circuit board substrate comprises a rigid or rigid-flexible base material.